Interleukin-17 Can Be the Target of Novel Treatment Strategies for Particulate Matter-Induced Allergic Diseases.

Air pollution is the single most significant environmental health risk.1 Data from the World Health Organization (WHO) show that more than 90% of people worldwide breathe polluted air.2 Particulate matter (PM), one of the most important components of air pollution, has a significant impact on human health and well-being. PM contributes to the onset and aggravation of asthma and allergic diseases.3 The Europe 2021 report shows that most urban dwellers were exposed to concentrations of fine PM (PM2.5; 97% of the dwellers) and coarse PM (PM10; 81%) above WHO recommendations.4 Numerous epidemiological studies have demonstrated the link between allergic diseases and PM.35 PM induces excessive reactive oxygen species production and induces mitochondrial damage and autophagy in bronchial epithelial cells through AMP-activated protein kinase.6 PM can change the epigenetics and microbiota in the airways.7 PM2.5 is more harmful than PM10 in terms of respiratory and allergic diseases and can reach the terminal part of the lung and systemic circulation.8

PM has electrostatic properties and can adhere to airborne allergens.3 PM can interact with aeroallergens and promote airway sensitization by modulating the allergenicity of airborne allergens.3 Several studies have reported the molecular mechanism of PM-induced allergic diseases.9 It has been suggested that granulocyte-macrophage colony-stimulating factor, tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-8, IL-17, IL-23 and macrophage inflammatory protein-2 play a role in the development of PM-induced allergic and immunologic diseases.10 Although there are reports on strategies to prevent PM-induced allergic diseases such as avoidance behavior or reduction of PM production, a few studies are available on the treatment.910 However, the development of treatment strategies is important because avoidance behavior may have a limited effect depending on the environmental situation and reduction of PM production will take a long time, especially in underdeveloped countries.

In the current issue, Bae et al.11 propose that IL-17 is an essential mediator of PM-induced allergic conjunctivitis and allergic rhinitis. They also suggest an interesting treatment target for PM-induced allergic diseases using IL-17 pathways. Bae et al.11 exposed OVA/Poly(I:C) mouse models, whose Th-17-associated inflammatory response is greater than that of the conventional OVA/alum model, to micro-and nano-sized titanium dioxide (TiO2). Symptoms of allergic rhino-conjunctivitis and inflammatory parameters including IL-4, IL-17, and interferon-γ levels were analyzed. In particular, the role of IL-17 was investigated with IL-17-neuralizing antibody (IL-17Ab). They found that treatment with IL-17Ab significantly improved the tear break-up time in the eyes and the symptom score of sneezing and nasal rubbing. Immunohistochemical staining demonstrated that IL-17Ab decreased the levels of IL-17 and neutrophils in the eyes and the nose of the OVA/Poly(I:C) model. Histological staining showed that the levels of TNF-α and IL-1β in conjunctiva were decreased after IL-17Ab treatment.

IL-17 is secreted by Th17 cells and is a cytokine related to T-cell and neutrophil activation. IL-17 affects tissue cells and IL-17 receptors are expressed in all epithelial cells.12 IL-17 has related allergic responses and is elevated mainly in acute and severe forms of allergic diseases.1012 The IL-17 family consists of 6 members (IL17A to IL-17F). The IL-17 receptors, IL-17RA, IL-17RB/IL-25R, IL-17RC, IL-17RD/SEF, and IL-17RE, play a role in the development and exacerbation of allergic diseases.121314 Anti-IL-17 therapy has been proposed to be promising for asthma patients.15 IL-17 increases the levels of proinflammatory and profibrotic cytokines. Interestingly, IL-17 decreases the effect of glucocorticoid in the airway epithelium by inducing epigenetic changes and inflammatory cytokine production. In this regard, anti-IL-17 therapy may be important in severe and steroid-resistant bronchial asthma.15 Allergic rhinitis patients have a higher serum level of IL-17 than healthy controls.10 IL-17 is considered a new biological treatment target in inflammatory autoimmune or immune-mediated diseases.16 However, there is still controversy on the role of IL-17 in atopic dermatitis.17

Understanding the IL-17 pathway may provide a new strategy for the treatment of PM-induced allergic diseases. Further translational studies and clinical trials using anti-IL-17 therapy in the eyes and the ears are needed. Topical applications have fewer side effects and a higher therapeutic dosage than systemic applications in the eyes and the nose. Further studies about targeting IL-17 or another molecular target for PM-induced allergic diseases are expected.